Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase

Abstract

Compositions and methods are provided for treating diseases associated with aberrant silencing of gene expression such as cancer by reestablishing the gene expression through inhibition of DNA hypomethylation and histone deacetylase. The method comprises: administering to a patient suffering from the disease a therapeutically effective amount of a DNA methylation inhibitor such as a cysteine analog such as decitabine, in combination with an effective amount of histone deacetylase inhibitor such as hydroxamic acid, cyclic peptide, benzamide, butyrate, and depudecin.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]This invention relates to compositions and methods for using antineoplastic agents to treat diseases such as cancer, and more specifically, to compositions and methods for effectively treating these diseases through reestablishment of gene transcription with a combination therapy including a DNA methylation inhibitor and a histone deacetylase inhibitor.[0003]2. Description of Related Art[0004]The evolution of new therapies for diseases associated with abnormal cell proliferation such as cancer has provided many choices of therapeutics for clinical treatment. Recent development and FDA approval of biologic therapy for refractory tumors, such as melanoma, raises a new hope that more advances tumors that have been refractory to all approaches with conventional drugs may be curable by taking non-conventional approaches.[0005]Currently therapeutic agents used in clinical cancer therapy are categorized into six groups: alkyla...

AI Technical Summary

Benefits of technology

[0043]Also according to the present invention, after the treatment with the DNA methylation inhibitor and histone deacetylase inhibitor, the patient may be further treated with various anticancer agents such as alkylating agent, antibiotic agent, retinoid, antimetabolic agent, hormonal agent, plant-derived agent, anti-angiogenesis agent and biologic agent. Owing to the sensitizing effects of the combination therapy on the cells to apoptosis, the dosage of anticancer agents used for the treatment may be lower than that used in a convention cancer treatment regimen. Thus, a better clinical outcome may be achieved by using the compositions and methods of the present invention.

Problems solved by technology

The cancer cells sensitized by such a combination die quickly or become more prone to cell death signals sent by administration of conventional anti-neoplastic agents.

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